TY - JOUR
T1 - The neuropsychiatric phenotype in Darier disease
AU - Gordon-Smith, Katherine
AU - Jones, Lisa
AU - Burge, SM
AU - Munro, CS
AU - Tavadia, S
AU - Craddock, N
PY - 2010/9/1
Y1 - 2010/9/1
N2 - BACKGROUND: Darier disease (DD) is a rare autosomal dominantly inherited skin disorder in which co-occurrence of neuropsychiatric abnormalities has been frequently reported by dermatologists. It is caused by mutations in a single gene, ATP2A2, which is expressed in the skin and brain. OBJECTIVES: To conduct the first systematic investigation of the neuropsychiatric phenotype in DD. METHODS: One hundred unrelated individuals with DD were assessed using a battery of standardized neuropsychiatric measures. Data were also obtained on a number of clinical features of DD. RESULTS: Individuals with DD were found to have high lifetime rates of mood disorders (50%), specifically major depression (30%) and bipolar disorder (4%), and suicide attempts (13%) and suicidal thoughts (31%). These were more common in DD when compared with general population data. The prevalence of epilepsy (3%) in the sample was also higher than the prevalence in the general population. There was no consistent association of specific dermatological features of DD and presence of psychiatric features. CONCLUSIONS: These findings highlight the need for clinicians to assess and recognize neuropsychiatric symptoms in DD. The results do not suggest that neuropsychiatric symptoms are simply a psychological reaction to having a skin disease, but are consistent with the pleiotropy hypothesis that mutations in the ATP2A2 gene, in addition to causing DD, confer susceptibility to neuropsychiatric features. Further research is needed to investigate genotype-phenotype correlations between the types and/or locations of pathogenic mutations within ATP2A2 and the expressed neuropsychiatric phenotypes.
AB - BACKGROUND: Darier disease (DD) is a rare autosomal dominantly inherited skin disorder in which co-occurrence of neuropsychiatric abnormalities has been frequently reported by dermatologists. It is caused by mutations in a single gene, ATP2A2, which is expressed in the skin and brain. OBJECTIVES: To conduct the first systematic investigation of the neuropsychiatric phenotype in DD. METHODS: One hundred unrelated individuals with DD were assessed using a battery of standardized neuropsychiatric measures. Data were also obtained on a number of clinical features of DD. RESULTS: Individuals with DD were found to have high lifetime rates of mood disorders (50%), specifically major depression (30%) and bipolar disorder (4%), and suicide attempts (13%) and suicidal thoughts (31%). These were more common in DD when compared with general population data. The prevalence of epilepsy (3%) in the sample was also higher than the prevalence in the general population. There was no consistent association of specific dermatological features of DD and presence of psychiatric features. CONCLUSIONS: These findings highlight the need for clinicians to assess and recognize neuropsychiatric symptoms in DD. The results do not suggest that neuropsychiatric symptoms are simply a psychological reaction to having a skin disease, but are consistent with the pleiotropy hypothesis that mutations in the ATP2A2 gene, in addition to causing DD, confer susceptibility to neuropsychiatric features. Further research is needed to investigate genotype-phenotype correlations between the types and/or locations of pathogenic mutations within ATP2A2 and the expressed neuropsychiatric phenotypes.
U2 - 10.1111/j.1365-2133.2010.09834.x
DO - 10.1111/j.1365-2133.2010.09834.x
M3 - Article
C2 - 20456342
SN - 1365-2133
SN - 1365-2133
SN - 1365-2133
SN - 1365-2133
SN - 1365-2133
SN - 1365-2133
SN - 1365-2133
SN - 1365-2133
SN - 1365-2133
SN - 1365-2133
SN - 1365-2133
SN - 1365-2133
SN - 1365-2133
SN - 1365-2133
SN - 1365-2133
SN - 1365-2133
VL - 163
SP - 515
EP - 522
JO - British Journal of Dermatology
JF - British Journal of Dermatology
IS - 3
ER -